"The world is moving towards a post-antibiotic era where common infections will kill again.
"If the current trend continues, sophisticated interventions such as organ transplants, joint replacements, chemotherapy and care of premature babies will become more difficult or even too dangerous to perform.
"It could also lead to the end of modern medicine as we know it."
This was stated by the then Director General of the World Health Organization when she appeared before the United Nations in April 2016.
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Dr. Margaret Chen wanted to raise awareness of what many considered the greatest threat to global health: the growing problem of infections that do not respond to antibiotic treatment.
It sounds panicky, but maybe not panicky enough.
The effectiveness of the world's antibiotics is in rapid decline - the drugs we use to treat infections are working less and less.
If we continue at this rate without intervention, we may run out of antibiotics to treat any type of bacterial infection.
"It would really change life as we know it," says Dr. David Weiss, director of Amory University's Center for Bacterial Antibiotic Resistance.
"Just imagine if we went back to an age where a minor accident like a scratch could lead to death," he adds.
A world with complete resistance of bacteria to antibiotics could lead to this.
But there is also good news: we will most likely not continue at this pace.
The world is aware of the problem and there are many organizations, governments and concerned citizens working hard to avoid the worst possible scenario.
The bad news is that the problem is extremely complex and widespread.
And thanks to the very nature of bacteria and the way they work - and the damage we've already done - the world will never again be completely devoid of that resistance.
What is resilience?
Imagine, for example, that you get infected with staph.
In the past, this was easily treated with penicillin, but today it's very possible that your staph infection is actually MRSA - the antibiotic-resistant version (only 10 percent of current staph infections are not MRSA).
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Penicillin is helpless against it. Moreover, studies show that two out of every 100 people carry the MRSA bacteria around.
Here's how resistance develops: Just like humans, bacteria have DNA. And just like in humans, that DNA can mutate or change.
Then, when the outside world comes into contact with those mutations, survival of the fittest means that only the strongest variations will survive.
This will truly change life as we know it.
And because when people use antibiotics to kill bacteria, in some cases the genes of those bacteria spontaneously mutate, which changes their composition and thus the antibiotics cannot kill them.
Bacteria that survive these encounters pass these genes on to other bacteria through the most common of matings (technically known as 'conjugation') - and these resistant bacteria can pass from one living thing to another.
Abuse of antibiotics in Serbia and how to combat it
There is a "great abuse" of antibiotics in Serbia, and it culminated in the past few months due to the corona virus pandemic, Dr. Tanja Aleksić, internist at the Health Center in Pančevo, told the BBC in Serbian.
"Patients are unhappy when you don't prescribe an antibiotic, because they often mistakenly believe that it is the only solution for respiratory infections.
"Antibiotics in Serbia are taken as 'candies' - this can lead to such resistance of bacteria to antibiotics, that we will not be able to treat bacterial infections in the future, and that scares me," the doctor points out.
About 65 percent of respondents who participated in the survey this year City Institute for Public Health Belgrade used antibiotic therapy during the previous 12 months of participation in the study.
In 56 percent of cases, the therapy was prescribed by a doctor, and 20 percent of respondents took antibiotics independently and without a doctor's advice, it added.
58 percent of the respondents used antibiotic therapy as prescribed by the doctor, but the research showed that 18 percent do not follow the doctor's recommendations and stop the therapy as soon as they feel improvement, according to the results of the research of the City Public Health Institute.
Almost two-thirds (63 percent) of the participants in the survey said that they keep a supply of antibiotics in their home pharmacy, according to the survey data.
"Purchasing antibiotics is legally regulated and requires a prescription, but it is still insufficiently respected," added Dr. Aleksić.
The Ministry of Health of the Republic of Serbia issued in November 2018 A new national guideline for the rational use of antibiotics in order to help doctors in prescribing this type of medicine and help the global fight against antimicrobial resistance.
Patients generally mistakenly think that viral infections can be cured faster with antibiotics and feel safer if they drink them, says Aleksić.
"It is partly the doctor's fault - most patients to whom you explain that an antibiotic cannot cure a viral infection accept it.
"Education is therefore very important - with younger people it goes easier, they understand and accept when you explain it to them, while it is much more difficult with the elderly," she concludes.
The nasty part about all of this is that bacteria can share genes with each other across the bacterial world - they don't even have to be too genetically similar to pass on resistance.
Humans and animals, which are full of trillions of different types of bacteria, then pass the resistant bacteria to each other.
And, in addition to all this, we introduce these resistant species to each other in our own bodies.
So even people or animals that are exposed to an antibiotic only once in their life can harbor mutated bacteria that can easily spread further.
Bacteria, it turns out, don't care about political borders or immigration policies—for example, researchers have even found drug-resistant bacteria on the tails of seagulls in Lithuania and Argentina.
The most important part of all of this is that bacterial resistance is essentially a numbers game: the more people try to kill bacteria with antibiotics and the more different antibiotics are used, the more opportunities bacteria will have to develop new genes to resist those antibiotics.
The less we use them, the less bacteria can share that resistance.
How big of a problem is this?
It's hard to say for sure, but the US Centers for Disease Control and Prevention (CDC) estimates that in the US alone, there are about 23.000 people who die each year from infections caused by antibiotic-resistant bacteria.
For example, they estimate that resistance to antibiotics that treat Clostridium difficilee leads to nearly 500.000 infections in the U.S. each year, ultimately resulting in approximately 15.000 deaths.
But Amanda Dzezek, a spokeswoman for policy and government relations at the Infectious Diseases Society of America, says the total number of deaths is a fairly modest estimate and is likely much higher in reality.
Meanwhile, a 2015 study published in the journal Nature found that global antibiotic use jumped 30 percent between 2000 and 2010.
WHO estimates that in the case of tuberculosis alone, there are 480.000 people worldwide with drug-resistant strains of the disease.
In 2014, they estimated that 3,3 percent of all new tuberculosis cases are resistant to multiple drugs, and in cases that return, up to 20 percent are resistant.
They also tracked cases of resistance (some very common, some less so) to drugs used to treat Escherichia coli, urinary tract infections, HIV, gonorrhea, malaria, pneumonia, and staphylococcal infections (of which the MRSA version is drug-resistant). .
And according to Public Health England, "the British government considers the threat of bacterial resistance to antibiotics as seriously as a flu pandemic or a mass flood."
If left to run wild, bacterial resistance to antibiotics could lead to 10 million deaths worldwide by 2050, at a cost of £66 trillion.
How did we get here?
In the simplest terms, humanity has drastically overused antibiotics.
Not only have doctors for decades handed out antibiotics by the handful to any patient who asked for them (regardless of whether they actually needed them or not), some countries still consider antibiotics to be over-the-counter drugs - as easy to buy as Anadin or tylenol.
Most of Europe tends to use three times more antibiotics than some other European countries such as Sweden or the Netherlands, where they are used only occasionally, according to Dr. Mark Sprenger, director of the antimicrobial program.
"It has nothing to do with more people getting sick. It's a cultural phenomenon," he says.
In addition, agricultural development around the world has fed antibiotics to livestock and food-producing animals for decades - not only as a way to reduce infection, but also as a method of promoting growth.
Although humans do not ingest these antibiotics, they do ingest the bacteria that live in these animals.
So if those animals carry drug-resistant bacteria, so could you, potentially.
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Until recently, antibiotics in the US listed animal growth as an indication for use on antibiotic labels, and farmers did not need a prescription to obtain them.
To illustrate how big a problem this is: just in November 2016, a strain of Escherichia coli found in Chinese pigs was found to be resistant to colistin.
It is an antibiotic that was used in the US only in the most severe cases of human infection, untreatable by other antibiotics.
In less than six months, the CDC detected that strain of E. coli in a patient in Pennsylvania.
So why not just make new antibiotics that bacteria won't be resistant to?
It has been several decades since a pharmaceutical company developed and sold a new antibiotic.
"You'd love to have new antibiotics to treat infections with resistant bacteria, but if you look at the timeline of new drug releases, it's been empty for almost 30 years," says Sprenger.
This is because the process of creating any new drug is extremely expensive, and the possible profit from antibiotics after such a massive investment is relatively small.
"There are no legal instruments to ban the use of a new antibiotic," Sprenger points out.
This means that if a new antibiotic comes out, there is no way to stop the world from overusing it.
At the current level of use of the new antibiotic, he says, the antibiotic would only have two years of life on the market before bacterial resistance to it would develop.
How do we get out of this?
First, the whole world must participate.
This practically happened in 2015 when WHO member countries agreed to accept the Global Action Plan - at that moment, bacterial resistance to antibiotics was already a problem that had been known for decades.
The plan outlined comprehensive solutions and best practices that all countries can take to reduce resilience.
"It's a historic thing," says Sprenger.
Before that, he says, the only people actively discussing how to reduce resistance were mostly people in medical circles.
"Ninety-five percent of the world's population now lives in a country where there is a developed national action plan. All these countries have stepped up activities in education, training and prevention control."
Then, last year, the UN addressed this problem at the General Assembly - only the fourth time in history that a health issue was discussed at that place.
And in May 2017, G20 leaders signed a declaration on global health that includes addressing the problem of antibiotic resistance.
So it's definitely a huge challenge that world leaders have started to take very seriously.
The largest part of the WHO action plan deals with hospital management and supervision.
The CDC began working closely with US hospitals to provide guidelines and education for safe and rational antibiotic prescribing.
"We have made some progress," says Dr. Catherine Fleming-Dutra, an epidemiologist from the US.
"Over the last few decades, we have seen a decline in antibiotic prescribing for children in the US. We have less progress with adults. - the rate among adults remained relatively unchanged," she adds.
Once hospitals and doctors begin to reduce prescriptions, the next step is to change the regulations regarding agriculture.
In 2007, the European Union banned antibiotics as growth promoters in animals.
In January 2017, the US Food and Drug Administration (FDA) removed growth from the listed antibiotic use on drug labels.
"There was a genuine understanding among farmers that this is something they need to take seriously and act on."
We're encouraged that they listened to us and worked with us to find a way to make it work," said Dr. William Flynn, deputy director of science policy at the FDA's Center for Veterinary Medicine.
But other countries need to follow suit - as can be seen from the relatively recent revelations about the resistance of bacteria to antibiotics coming from China.
One of the most important steps in dealing with resilience is tracking it. The CDC has devised a system called the National Antimicrobial Surveillance System (NARMS).
"Surveillance of antibiotic-resistant bacteria is a big part of our mission," says Dr. Jean Patel, deputy director of the CDC's Office of Antibiotic Resistance.
"We do this to measure the burden of infection, but also to characterize the types of resistance we encounter. This helps us strategize how best to prevent resistance," she points out.
We won't be able to stop it completely, claims Amanda Džezek, vice president of public policy and government relations at the Infectious Diseases Society of America.
"Even the correct use of antibiotics contributes to the development of resistance," explains Jezek.
The CDC is funded by state health departments across the US (and coordinates with laboratories worldwide) to maintain a network of data and samples of antibiotic-resistant bacteria.
"We can use that to have national estimates of infection rates and to see how these bacteria are changing, to test new drugs against the bacteria, and we'd use the bacteria that we've collected in this way to help make vaccines." according to Patel.
But some non-traditional methods are also being tried.
Amory University in Atlanta, Georgia, has established a unique Center for Bacterial Antibiotic Resistance.
One of its main goals is to make diagnostic tests using mutated bacteria collected by the national surveillance system and doctors in their clinics who can spot resistant bacteria.
"The goal is to have scientists, doctors and epidemiologists working together to solve this problem," says center director David Weiss.
It's something that didn't happen normally - there was a schism between what scientists and doctors were doing, he explains.
"I'm not a doctor and I need to find out from doctors what they see on the front line, which would help make our research as relevant as possible," adds this expert.
A comprehensive, collaborative approach could work: England's National Health Service announced in 2016 that it had reduced antibiotic prescribing by 2015 percent in 5,3 compared to 2014.
Public Health England says more responsible prescribing is key: it says it advised the NHS in 2015 to undertake better practice aimed at reducing antibiotic prescribing by 10 per cent from 2013 levels.
And finally, there must be initiatives that encourage the development of new antibiotics.
The US National Institutes of Health and the Biomedical Advanced Research and Development Administration have organized a biopharmaceutical accelerator called CARB-X.
The fund allocates 48 million dollars to support projects to discover new antibiotic drugs.
"They work with companies in the very early stages of discovery to provide funding and technical support to get them to the point where they have a product that they can start clinical trials with," says IDSA's Dzezek.
In the same vein, IDSA is also working to develop legislation that would provide funding for clinical trials so that companies can avoid huge costs and have a chance to make some money from new antibiotics.
With all these programs coming together and with similar efforts being implemented around the world, there is great hope that humanity will be able to solve this problem.
However, “we can only slow down the progress of resilience. We won't be able to stop it completely," says Džezek.
"Even the correct use of antibiotics contributes to the development of resistance."
And that means the challenge will always remain huge.
As long as there are people, and those people carry and transmit diseases - which they will do - the whole world will have to continue the fight against resistance.
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